1. Field of the Invention
The present invention relates to an implantable sensor chip for detecting a constituent level or condition, and more particularly to a sensor chip which includes living cells sensitive to the constituent level or condition, which are grown on a fabricated sensor substrate.
2. Description of the Related Art
Normally, cells have a constant potential difference across the membrane of the cell. Many types of living cells, however, generate electric signals under particular conditions or in the presence of particular constituents to which the cells are sensitive. These signals usually appear as voltage or potential spikes which are of relatively short duration. The amplitude of these voltage spikes is on the order of 0.1 V and the duration of the spikes varies from about 1 ms to 1 s. These electrical signals or spikes can be directly related to a major function of the cells, for example, in nerve cells, or they can be caused by some other activity, for example, cardiac muscle activity.
When these signals appear across the cell membrane, they may be recorded by introducing a first microelectrode into the cell, by providing a second electrode in the medium surrounding the cell, and by measuring the potential difference between the electrodes. However, the electric potential or electric field generated by an individual cell undergoing voltage spikes as recorded by external electrodes tends to be very small. Therefore, in practice, only fields generated by relatively large masses of cells that are firing simultaneously may be recorded, i.e., EEG, ECG, EMG, etc.
Commonly owned U.S. Pat. Nos. 5,101,814 and 5,190,041, and U.S. patent application Ser. No. 08/077,893, now U.S. Pat. No. 5,368,028, the contents of which are incorporated herein by reference, disclose methods by which the electrical activity of living cells encapsulated in a bio-compatible semi-permeable membrane may be measured. This electrical activity may be used to determine the concentration of various constituents or conditions in the medium that surrounds the cells or capsule. These electrical signals can be measured by electrodes within the membrane capsule, or in its vicinity outside the capsule. By implanting the capsule under a patients skin, it is impossible to determine the concentration of a predetermined constituent (e.g., glucose level) or a predetermined condition (e.g., blood pressure) in the region (e.g., adjoining tissue or blood vessel) in which the capsule is implanted.
All of the prior art devices measure the combined electrical activity of large cell masses. An object of the present invention is to enable individual cells rather than groups of cells to be used for detection of physical conditions or constituents by detecting the electrical signals generated by the individual cells. A further object of the invention is to detect the electrical signals without penetrating the cells with micro electrodes, which is not practical for long term in-vivo measurements.